Tumor is one of the major diseases that seriously endanger human life and health, and it is the abnormal proliferation and differentiation of cells. Experts of WHO predict that in 2020 the global population of cancer incidence will reach 20 million, the death toll will reach 12 million, and the cancer will become the number one killer of human beings in this century and the most serious threat to human survival. Incidence and mortality rates of lung cancer, colorectal cancer, gastric cancer and liver cancer rank in the top five positions among all types of malignant tumors.
According to data from “2012 Chinese Cancer Registry Annual Report”, released by the National Cancer Registry, new tumor cases for each year is about 3,120,000, an average of 8, 550 people per day, 6 people per minute in the country are diagnosed with cancer. Lung cancer, gastric cancer, colorectal cancer, liver cancer and esophageal cancer, are ranking in the top five in the national malignant tumor incidence. With the increase of incidence and mortality of malignant tumor, the demand for treatment of malignant tumor is increasing.
Chemotherapy is one of the effective methods for treatment of tumor. Basically, the mechanism of traditional chemotherapy drugs is preventing synthesis of deoxyribonucleic acids (DNA), ribonucleic acids (RNA) or proteins, or directly impacting on these macromolecules, thereby inhibiting the proliferation of cancer cells, then to death. Some drugs are also capable of inhibiting tumor growth by altering the balance of hormones in the human body. At present, anti-tumor drugs have been developed into 6 categories: anti-metabolism drugs; alkylating agents; cell toxin antibiotics; plant alkaloids and other natural drugs; antineoplastic hormones; and platinum and other anti-tumor drugs. With the change of clinical treatment models and discovery of some new anticancer drug targets, great changes have taken place in the field of anti-tumor drugs: mechanism of the drugs, has been transformed from traditional nonspecific cytotoxic drugs into noncytotoxic targeted drugs. In anti-tumor drugs approved by FDA in 2012, small-molecule tyrosine kinase inhibitor (TKI) has become the most popular research in the anti-tumor drugs, especially those targeting to multiple targets (about ¾), as of June 2013, the type of TKI approved by US FDA has reached 18. In addition, other drugs having hot mechanisms include immune stimulants, angiogenesis inhibitors, cell cycle inhibitors, immune inhibitors and stimulants, protein kinase inhibitors and the like.
Microbial and viral DNA in the infected mammalian cells can induce endogenous potent immune responses by stimulating interferon secretion. The endoplasmic reticulum (ER) receptor protein (STING) is an essential factor in the immune response to cytosolic DNA. Recent studies show that the cyclized cGMP-AMP dinucleotide synthetase (cGAS) after bonding with DNAs under activation conditions can endogenously catalyze the synthesis of cGAMP. cGAMP is a cytoplasmic DNA sensor, which is used as a second messenger to stimulate the induction of INF-ß by STING, to mediate the activation of TBK1 and IRF-3, and then to start the transcription of INF-ß gene. The recent reports show that, recombinant cGAS can catalyze cyclization of cGMP-AMP dinucleotide GAMP under the DNA binding conditions. The crystal structure of the complex of cGAS bonded with 18 bp dsDNA has also been reported, and a study of cGAMP in antiviral immunity has been confirmed. cGAMP bonded with STING, makes transcription factor IRF3 activated and generates ß interferon.